**4.1 Roles**

*Type 2 Diabetes - From Pathophysiology to Cyber Systems*

vitamin B12) malabsorption [38].

medication [40].

patients [42].

group [43].

**4. Folate, folic acid or B9**

cancer and senile dementia [41].

motility and increased growth of bacteria [37]. Celiac disease can be greatly widespread autoimmune mediated gastrointestinal state happen within 1–16% people having type 1 diabetes in contrast to 0.3–1% of common people. Intake for wheat gluten as well as further associated proteins is recognized as activator for situation within genetically liable persons. Because of linked enteropathy, people frequently stop to thrive, anemia and chronic diarrhea owing to micronutrient (mainly folate,

**3.2 Metformin stimulated vitamin B12 deficiency amongst patients with T2DM**

Due to lack for contradictions such as renal as well as hepatic dysfunction, current guiding principles support utilization of metformin like primary line glucose reducing mediator parallel to changes in way of life [39]. Regardless of better glycemic reducing influence, metformin is revealed for reduction of vitamin B12 status. The possibility for having metformin coupled vitamin B12 deficit can be deeply affected of growing age, metformin dosage as well as period of use. The given methods for clarification of metformin induced vitamin B12 shortage amongst people having type 2 diabetes comprise: variations of small bowel motility that induces increased growth of bacteria as well as resulting vitamin B12 deficit, viable reduction and vitamin B12 malabsorption, changes within intrinsic factor status as well as contact to tubulin endocytic receptor. Metformin hamper calcium bound assimilation for complex of vitamin B12-IF at the terminal ileum. Such inhibition consequence could be inverted using calcium

The term folate includes 150 components of the family of pteroilglutamate, which participate in cell replication by enzymatic activity in purine base synthesis for DNA and are a primary co-factor for transamination in the transformation of amino acids, particularly homocysteine into methionine. Folates are present in animal tissue, leafy vegetables, legumes and nuts and their deficiency has been associated to megaloblastic anemia, neural tube defects, cardiovascular disease,

Implication of folate in pathogenesis of type 2 DM is linked with vitamin B12 shortage and its consequent hyperhomocysteinemia, and although its deficiency is not widespread, supplementation trials have been carried out in diabetic

Folates are made up of 4[(2-amino-4-oxo-1,4-dihydropteridin-6-yl) methylamino] benzoic acid, pteroic acid which is bonded with multiple or single monomers of L-glutamate. They lie in the family of heterocyclic organic compounds

There are eight different types of B vitamins. They are collectively called as B complex vitamins. Folate i.e., Vitamin B9 is also one of them. The naturally present folate forms are also based on vitamin B9. Many of the foods contain B vitamins. Many of folates are also taken from foods. They are generally made up of a mix of reduced folates. Reduced folates are any type of pteroyl mono glutamates, or an amalgam of pteroyl glutamates. They have a peculiar degree of pteridine ring reduction. Also, they have a different number of glutamates remains and one-carbon replacements [44]. The seven of total eight B vitamins can dissolve in water and hence cannot be kept by our body. We must constantly get their supply in our daily diet. Folates (vitamin B9) have that property. We can get them from

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Folic acid is considered to be an essential nutrient for our body. Folic Acid derivatives are necessary components for the DNA production. They are also needed for the erythrocyte synthesis. The biosynthesis of some amino acids needs tetrahydrofolates as a crucial ingredient. They are needed in the biosynthesis of precursors of DNA also [48]. Folic acid is necessary for the production of deoxyribose nucleic acid (DNA). They even aid maintenance of the process of methylation [49]. They also participate as helper molecules in some biological reactions. The cell division in our body essentially needs folate. We need it even more during pregnancy and infancy. It is needed in multiple crucial processes like quick cell growth and proliferation. The production of RBCs also needs folate. This acts to keep from anemia [50]. Nucleotide synthesis is the most important function of folate. It is required for the production and repair of DNA. Folates are also responsible of the production of methionine by alteration of Homocysteine in the procedure of re-methylation. Methionine is a useful amino acid which is in turn used to produce other necessary proteins. It may get converted to an important methyl donor i.e., S-adenosylmethionine [51].

### **4.2 Inadequacy**

The deficiency of folate is not common in developed countries. But it is reported in many of the third-world countries. Folate deficiency could be due to multiple reasons. The poor diet and erroneous metabolism of vitamins could be responsible for it [52]. The US government along with that of many other countries has made fortification of food with folate to be mandatory for their nationals. This helps in eradication of NTDs worldwide. Mostly they use floor for the fortification because it is widely used by the public. The routine ingestion of folate is examined by taking the blood samples and measuring the folate levels in them. If the level of folate is low in blood samples then it means the folate is not taken up to required level [51].

We can fulfill our folate requirement by taking folate fortified diet. Artificial folate supplements are also available in the market which can serve the purpose. But the availability of any of the options of folate intake vary in different regions of world. The folate absorption also differs for every supplement used. Dietary Folate Equivalent (DFE) is the amount of folate our body can absorb out of the supplement taken per serving. Every DFE unit is considered to be one micro gram of folates or 0.6 micro grams of artificially made folate [50].

Loss of appetite along with decrease in body weight may occur due to deficiency in folate. The deficiency might be faced when one's need of folate increases or diet is reduced from a certain level. It is reported as a key health issue in some countries. Though it is rare in developed countries which enforce folate fortification of foods. Folate and vitamin B12 deficiency impacts all public of all ages. It is related to many diseases like neural tube defects in infants, diarrhea, anemia and other birth defects etc. [52].

The loss of methyl groups from DNA is termed as DNA hypomethylation. This could be affected by the deficiency of folate. The folate ingestion can fix such problems [53]. The overall methylation and DNA synthesis processes could also be negatively affected by the deficiency of folate in human body. Thymidyl acid, dTMP (Deoxythymidine monophosphate), is used as a monomer in DNA. Its supply in body becomes limited due to increased rate of removal of dUMP (Deoxy uridine Monophosphate) from the molecule of DNA. This is increased due to defective methylation cycle as a result of folate deficiency. DNA repair reactions start due to these problems which in turn declines the required cell division [45].

#### **4.3 Metabolism of folate (vitamin B9)**

Folic acid is inactive biochemically, it is transformed by dihydrofolate reductase into methyl tetrahydrofolate and tetrahydro folic acid. These folate congeners are carried by receptor-mediated endocytosis through body cells. There they are required to generate and use format, and synthesize thymidylate nucleic acids and purine, methylate tRNA, keep general erythropoiesis, interconvert amino acids. Utilizing vitamin B12 as a helper enzyme, folate can standardize high homocysteine quantities by re-methylation of homocysteine to methionine via methionine synthetase [16].
